Lung injury induced by different negative suction pressure in patients with pneumoconiosis undergoing whole lung lavage.

BACKGROUND: Pneumoconiosis is a diffuse interstitial fibronodular lung disease, which is caused by the inhalation of crystalline silica. Whole lung lavage (WLL) is a therapeutic procedure used to treat pneumoconiosis. This study is to compare the effects of different negative pressure suction on lung injury in patients with pneumoconiosis undergoing WLL. MATERIALS AND METHODS: A prospective study was conducted with 24 consecutively pneumoconiosis patients who underwent WLL from March 2020 to July 2020 at Emergency General Hospital, China. The patients were divided into two groups: high negative suction pressure group (group H, n = 13, negative suction pressure of 300-400 mmHg) and low negative suction pressure group (group L, n = 11, negative suction pressure of 40-50 mmHg). The arterial blood gas, lung function, lavage data, oxidative stress, and inflammatory responses to access lung injury were monitored. RESULTS: Compared with those of group H, the right and left lung residual were significantly increased in the group L (P = 0.04, P = 0.01). Potential of hydrogen (pH), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), lactic acid (LAC) and glucose (GLU) varied from point to point in time (P < 0.01, respectively). There was statistical difference in the trend of superoxide dismutase (SOD) and interleukin-10 (IL-10) over time between the two groups (P < 0.01, P = 0.02). In comparison with the group H, the levels of IL-10 (P = 0.01) and SOD (P < 0.01) in WLL fluid were significantly increased in the group L. There was no statistical difference in the trend of maximal volumtary ventilation (MVV), forced vital capacity (FVC), forced expiratory volume in one second (FEV1%), residual volume (RV), residual volume/total lung capacity (RV/TLC), carbon monoxide dispersion factor (DLCO%), forced expiratory volume in one second/ forced vital capacity (FEV1/FVC%) over time between the two groups (P > 0.05, respectively). CONCLUSION: Low negative suction pressure has the potential benefit to reduce lung injury in patients with pneumoconiosis undergoing WLL, although it can lead to increased residual lavage fluid. Despite differing suction strategies, pulmonary function parameters including FEV1%, RV and DLCO% became worse than before WLL. Trial Registration Chinese Clinical Trial registration number ChiCTR2000031024, 21/03/2020.

Characteristics of SlCML39, a Tomato Calmodulin-like Gene, and Its Negative Role in High Temperature Tolerance of Arabidopsis thaliana during Germination and Seedling Growth.

Calmodulin-like (CML) proteins are primary calcium sensors and function in plant growth and response to stress stimuli. However, so far, the function of plant CML proteins, including tomato, is still unclear. Previously, it was found that a tomato (Solanum lycopersicum) CML, here named SlCML39, was significantly induced by high temperature (HT) at transcription level, but its biological function is scarce. In this study, the characteristics of SlCML39 and its role in HT tolerance were studied. SlCML39 encodes a protein of 201 amino acids containing four EF hand motifs. Many cis-acting elements related to plant stress and hormone response appear in the promoter regions of SlCML39. SlCML39 is mainly expressed in the root, stem, and leaf and can be regulated by HT, cold, drought, and salt stresses as well as ABA and H2O2. Furthermore, heterologous overexpression of SlCML39 reduces HT tolerance in Arabidopsis thaliana at the germination and seedling growth stages. To better understand the molecular mechanism of SlCML39, the downstream gene network regulated by SlCML39 under HT was analyzed by RNA-Seq. Interestingly, we found that many genes involved in stress responses as well as ABA signal pathway are down-regulated in the transgenic seedlings under HT stress, such as KIN1, RD29B, RD26, and MAP3K18. Collectively, these data indicate that SlCML39 acts as an important negative regulator in response to HT stress, which might be mediated by the ABA signal pathway.

[A Maternal Health Care System Based on Mobile Health Care].

Wearable devices are used in the new design of the maternal health care system to detect electrocardiogram and oxygen saturation signal while smart terminals are used to achieve assessments and input maternal clinical information. All the results combined with biochemical analysis from hospital are uploaded to cloud server by mobile Internet. Machine learning algorithms are used for data mining of all information of subjects. This system can achieve the assessment and care of maternal physical health as well as mental health. Moreover, the system can send the results and health guidance to smart terminals.

The cumulative live birth rate of recombinant follicle-stimulating hormone alfa verse urinary human follicle-stimulating hormone for ovarian stimulation in assisted reproductive technology cycles.

BACKGROUND: Infertility remains a significant public health concern. An issue with controlled ovarian stimulation (COS) is the selection of an exogenous gonadotropin (Gn) regimen, which is mainly based on urinary follicle-stimulating hormone (uFSH), recombinant follicle-stimulating hormone alfa (rFSH-alfa), and human menopausal gonadotropin (HMG). In addition, most previous studies focused on the clinical pregnancy rates or live birth rates (LBR) per transfer cycle, but not on the cumulative live birth rate (CLBR) per started cycle. The CLBR, appears to be a more comprehensive and accurate universal measure of IVF treatment success. Therefore, this study aimed to compare the cumulative live birth rate (CLBR) between rFSH-alfa and uFSH regimens for ovarian stimulation. METHODS: This retrospective cohort study included patients who underwent assisted reproductive technology (ART) with gonadotropin-releasing hormone (GnRH) agonist long protocol between March 2009 and December 2018. Patients were grouped according to the Gn regimen received (rFSH-alfa or uFSH). The main outcome was CLBR, which defined as the first live birth following the use of all fresh and frozen embryos derived from a single COS cycle. RESULTS: A total of 1078 cycles were analyzed (314 with rFSH-alfa and 764 with uFSH). The rFSH-alfa group was characterized by a higher number of retrieved oocytes (13.3 vs. 11.0) and transferable embryos (5.0 vs. 4.0), a higher fresh embryo transfer rate (35.0% vs. 26.3%), and a higher multiple birth rate among the fresh embryo transfer cycles (8.2% vs. 2.5%) (P < 0.05). There were no differences in pregnancy rate (32.7% vs. 33.8%) and LBR (25.5% vs. 26.9%) per transfer cycle (P > 0.05). No significant difference was found in clinical outcomes among the frozen embryo transfer cycles (P > 0.05). The CLBR per started cycle in the rFSH-alfa group was higher than in the uFSH group (53.5% vs. 43.1%, P < 0.05). After adjustment, rFSH-alfa was independently associated with a higher CLBR (OR = 1.56; 95%CI = 1.18-2.05; P = 0.0018). CONCLUSIONS: rFSH-alfa and uFSH have similar pregnancy rates and LBR per transfer cycle, rFSH-alfa might achieve more transferrable blastocysts and higher CLBR per started cycle compared to uFSH.

Genome-Wide Identification of the Bcl-2 Associated Athanogene (BAG) Gene Family in Solanum lycopersicum and the Functional Role of SlBAG9 in Response to Osmotic Stress.

The Bcl-2-associated athanogene (BAG) proteins are a family of multi-functional group of co-chaperones regulators, modulating diverse processes from plant growth and development to stress response. Here, 10 members of SlBAG gene family were identified based on the available tomato (Solanum lycopersicum) genomic information and named as SlBAG1-10 according to their chromosomal location. All SlBAG proteins harbor a characteristic BAG domain, categorized into two groups, and SlBAG4, SlBAG7, and SlBAG9 of group I contain a plant-specific isoleucine glutamine (IQ) calmodulin-binding motif located in the N terminus. The quantitative real-time PCR expression analysis revealed that these SlBAG genes had organ-specific expression patterns and most SlBAG genes were differentially expressed in multiple abiotic stresses including drought, salt, high temperature, cold, and cadmium stress as well as abscisic acid and H2O2. In addition, heterologous overexpression of SlBAG9 increased the sensitivity of Arabidopsis to drought, salt, and ABA during seed germination and seedling growth. The decreased tolerance may be due to the downregulation of stress-related genes expression and severe oxidative stress. The expression levels of some stress and ABA-related genes, such as ABI3, RD29A, DREB2A, and P5CS1, were significantly inhibited by SlBAG9 overexpression under osmotic stress. Meanwhile, the overexpression of SlBAG9 inhibited the expression of FSD1 and CAT1 under stress conditions and the decreased levels of superoxide dismutase and catalase enzyme activities were detected accompanying the trends in the expression of both genes, which resulted in H2O2 accumulation and lipid peroxidation. Taken together, these findings lay a foundation for the future study of the biological function of SlBAG genes in tomato.

Overexpression of a Bcl-2-associated athanogene SlBAG9 negatively regulates high-temperature response in tomato.

The Bcl-2-associated athanogene (BAG) gene is a multi-functional family of co-chaperones regulator, modulating plant stress response. Our previous study revealed that the SlBAG9 of tomato (Solanum lycopersicum) had the higher expression level induced by high-temperature (HT) at the transcriptional and protein levels, but its biological function was still unclear. Here, we conducted an in-depth analysis of SlBAG9. SlBAG9 protein was not located in the mitochondria but in the cytoplasm and nucleus. Many cis-acting elements involved in plant stress and hormone responses were located in the promoter regions of SlBAG9 including heat-shock element (HSE1). The ß-glucuronidase (GUS) histochemical analysis showed that SlBAG9 promoter could drive GUS gene expression in transiently transformed Nicotiana tabacum leaves under non-inducing condition and HSE1 is critical for HT-induced GUS activity under HT. The transcription of SlBAG9 was expressed in different organs and was regulated by HT, cold, drought, and salt stresses as well as exogenous abscisic acid (ABA) and H2O2. To further elucidate SlBAG9 function in response to HT, the transgenic tomato plants overexpressing SlBAG9 were developed. Compared to the wild-type plants, SlBAG9-overexpressing plants exhibited more sensitivity to HT stress, reflected by the burning symptoms, the degradation of chlorophyll, and the reduction of photosynthetic rates. Additionally, SlBAG9-overexpressing lines showed higher accumulation of lipid peroxidation production (MDA) and H2O2, but lower activities of superoxide dismutase, catalase, and peroxidase. Therefore, it is speculated that SlBAG9 plays a negative role in thermotolerance probably by inhibition of antioxidant enzyme system leading to the oxidative damage, consequently aggravating the HT-caused injury phenotype.

Correlations between elevated basal sperm DNA fragmentation and the clinical outcomes in women undergoing IUI.

Objective: This study aimed to explore the impact of the sperm DNA fragmentation index (DFI) on the clinical outcomes in women undergoing artificial insemination by husband intrauterine insemination (AIH-IUI). Methods: In this retrospective study, the value of sperm DFI was detected by sperm chromatin structure assay (SCSA) in a semen analysis collected before fertility treatment (basal DFI) in 1,500 IUI cycles at the infertility clinic of Northern Jiangsu People's Hospital Reproductive Medicine Center from Jan 2016 to April 2021. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value for the clinical outcomes of IUI, including the biochemical pregnancy rate, clinical pregnancy rate, delivery rate, and live birth rate, and multivariate logistic regression was conducted to analyse the risk factors for clinical outcomes after IUI. Result: In 1,500 IUI cycles, the results showed that there were no statistically significant differences between the normal DFI group and the abnormal DFI group in biochemical pregnancy rate (14.41% vs. 11.3%, P = 0.386), clinical pregnancy rate (12.9% vs. 10.5%, P = 0.433), delivery rate (11.0% vs. 8.9%, P = 0.456), live birth rate (10.9% vs. 8.9%, P = 0.484) or pregnancy loss rate (14.6% vs. 15.4%, P = 1.000). Conclusion: Sperm DFI alone may have limited predictive power for IUI clinical outcomes.

Promotion of the immunomodulatory properties and osteogenic differentiation of adipose-derived mesenchymal stem cells in vitro by lentivirus-mediated mir-146a sponge expression.

Mesenchymal stem cells (MSCs) exert beneficial effects on the repair of bone tissue via both immunomodulatory functions and osteogenic differentiation. As one of the first miRNAs identified that regulate innate immune responses, miR-146a has been reported to serve as a negative-feedback regulator in several chronic inflammatory diseases. However, the majority of studies focus on understanding how miRNA-146a regulates immune cells and the associated immune-based disorders. In the present study, we employed miRNA sponges that were forcibly expressed using a lentiviral vector to knock down the expression of miR-146a in human adipose-derived stem cells (hASCs). The hASCs transduced with miR-146a sponges exhibited enhanced immunomodulatory properties, as evidenced by the increased production of key immunosuppressive factors. These factors were able to elevated expression of anti-inflammatory genes and inhibited the expression of inflammatory genes in macrophages. Further mechanistic studies showed that the suppression of miR-146a activated NF-κB signaling in hASCs, suggesting its regulatory role in miR-146a sponge-induced immunomodulatory changes in hASCs. In addition, the suppression of miR-146a was also found to stimulate the osteogenic differentiation of hASCs. The observed upregulation of SMAD4 expression indicated the involvement of SMAD4 in modulating the osteogenic potential of hASCs in response to miR-146a suppression. Our study contributes to the understanding of the effects of miR-146a on the immunomodulatory properties and osteogenic differentiation of hASCs and highlights the potential use of miRNA-146a sponges modified hASCs as seed cells for bone tissue engineering.

Substrate stiffness affects the immunosuppressive and trophic function of hMSCs via modulating cytoskeletal polymerization and tension.

Mesenchymal stem cells (MSCs) have broad therapeutic potential due to their ability to secrete bioactive factors that are immunomodulatory and trophic (regenerative). In this study, polyacrylamide (PAAm) hydrogels with different stiffness are used as a model to explore the effects of substrate stiffness on the paracrine function of human mesenchymal stem cells (hMSCs). Human MSCs cultured on soft substrates produced significantly higher levels of immunomodulatory and trophic factors compared with hMSCs cultured on rigid substrates. The enhanced paracrine function of hMSCs is further confirmed by the M2 phenotypic polarization observed in macrophages, as well as the accelerated chemotactic migration and angiogenesis capacity observed in human umbilical vein endothelial cells (HUVECs) after treatment with conditioned media (CM) collected from hMSCs cultured on soft substrates. Furthermore, the inhibited secretion of immunosuppressive and trophic factors by hMSCs cultured on rigid substrates is largely rescued by treatment with Lat.A, a cytoskeletal polymerization inhibitor. Similar results are observed after treatment with either myosin (Blebbi) or ROCK (Y27632) inhibitors. These results demonstrate that substrate stiffness is a key modulator of the paracrine function of hMSCs and highlight the potential utility of promoting tissue repair through stiffness-regulated paracrine signaling in MSCs.

Regulation of an osteon-like concentric microgrooved surface on osteogenesis and osteoclastogenesis.

Topographical cues provided by micropatterns on material surfaces have been demonstrated to control multiple cell functions. However, the majority of currently studied micropatterns fail to recapitulate the key characteristics of an osteon, which is the structural unit of natural cortical bone. Thus, in the present study, a micropatterned polycaprolactone (PCL) surface comprising a series of concentric circular microgrooves was fabricated by combining photolithography with the melt-casting method to mimic the concentric structure of an osteon in a two-dimensional setting. By culturing mouse mesenchymal stem cells (mMSCs) and osteoclast progenitor cells (RAW264.7 cells) on the osteon-like concentric microgrooved surface, the effects of this micropatterned surface on the osteogenesis of mMSCs and the osteoclastogenesis of RAW264.7 cells were systematically investigated. Osteoclastogenic differentiation was significantly inhibited in RAW264.7 cells on the fabricated osteon-like concentric microgrooved surface compared to that on the parallel linear microgrooved and flat surfaces, as indicated by the downregulated expression of key osteoclast-specific function genes (TRAP, CATK and MMP9), the lower activity of TRAP and less formation of TRAP-positive multinucleated giant osteoclasts. Further investigation indicated that RANK-NFκB signaling may have been involved in mediating the inhibited osteoclastogenesis of RAW264.7 cells by the osteon-like concentric microgrooved surface. In addition, the osteon-like concentric microgrooved surface greatly modulated the osteoclastogenic-related paracrine secretion of mMSCs (RANKL, M-CSF and OPG), despite its small effect on the osteogenesis of mMSCs. This secretory profile was found to be able to effectively inhibit osteoclastogenesis in RAW264.7 cells, confirming the enhanced osteoclastogenesis inhibitory functions of mMSCs on the osteon-like concentric microgrooved surface. Our findings demonstrate the importance of the microgroove orientation and arrangement in affecting cellular behaviors and highlight the potential benefits of incorporating osteon-like concentric microgrooved patterns on the surface of scaffolds for bone repair.

Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysis.

Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments.